WO1998022118A1 - Compositions et methodes pour traiter des troubles gastro-intestinaux - Google Patents

Compositions et methodes pour traiter des troubles gastro-intestinaux Download PDF

Info

Publication number
WO1998022118A1
WO1998022118A1 PCT/US1997/021462 US9721462W WO9822118A1 WO 1998022118 A1 WO1998022118 A1 WO 1998022118A1 US 9721462 W US9721462 W US 9721462W WO 9822118 A1 WO9822118 A1 WO 9822118A1
Authority
WO
WIPO (PCT)
Prior art keywords
bismuth
milligrams
composition
days
group
Prior art date
Application number
PCT/US1997/021462
Other languages
English (en)
Inventor
Jonathan Davidson Kaunitz
Owen Rickford Carryl
Shin Tanaka
Original Assignee
The Procter & Gamble Company
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by The Procter & Gamble Company filed Critical The Procter & Gamble Company
Priority to HU9904073A priority Critical patent/HUP9904073A3/hu
Priority to EP97949569A priority patent/EP0941102A1/fr
Priority to CA002271381A priority patent/CA2271381A1/fr
Publication of WO1998022118A1 publication Critical patent/WO1998022118A1/fr
Priority to NO992468A priority patent/NO992468L/no

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/245—Bismuth; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants

Definitions

  • H. pylori Helicobacter pylori
  • H. pylori the difficulty in treating many patients suffering from such gastrointestinal disorders caused or mediated by H. pylori, and the potential for resistance with antibiotic-containing regimens, a continuing need exists for safe and effective treatments against H. pylori, preferably which would be effective as mass treatment therapies in large populations of H. pylori carriers.
  • compositions and methods have been discovered by the present invention for the treatment of gastrointestinal disorders caused or mediated by H. pylori comprising the administration of bismuth salts, (other than salts formed between an H2 receptor antagonist and a complex of bismuth with a carboxylic acid), and a non-steroidal anti- inflammatory drug.
  • the present invention also comprises the optional administration of
  • an object of the present invention is to provide safe and effective compositions and methods of treating gastrointestinal disorders caused or mediated by H. pylori.
  • the present invention relates to a composition for treating a gastrointestinal disorder caused or mediated by Helicobacter pylori comprising from about 50 milligrams to about 5000 milligrams, per day, of bismuth; a gastropathic amount of a non-steroidal anti-inflammatory drug; and pharmaceutically acceptable carriers.
  • the present invention also relates to a method for treatment of a human or lower animal subject having a gastrointestinal disorder caused or mediated by Helicobacter pylori comprising administering to the subject from about 50 milligrams to about 5000 milligrams of bismuth, per day, for from about 1 to about 42 days, and a gastropathic amount of a non-steroidal anti-inflammatory drug.
  • the present invention relates to methods and compositions comprising bismuth and a non-steroidal anti-inflammatory drug for treating a gastrointestinal disorder caused or mediated by Helicobacter pylori.
  • the inventions may optionally comprise therapeutically effective amounts of one or more antisecretory agents.
  • the compositions also comprise pharmaceutically acceptable carriers.
  • the present invention and the essential and optional components therein are described fully below.
  • H. pylori are spiral bacteria which reside in the stomach. When first identified in the early 1980s, H. pylori was referred to by the name Campylobacter pyloridis. In recent years, these bacteria have been implicated as a causative factor for gastritis, non- ulcerative dyspepsia, and various ulcers of the gastrointestinal tract. These organisms are described in detail in the following publications, all of which are incorporated herein by reference in their entireties: Korman, M.G., Tygat, G.N., "Helicobacter pylori and Peptic Ulcer", Scandinavian Journal of Gastroenterologv. Suppl., 210:92-96 (1995); Marshall, B.
  • gastrointestinal disorder encompasses any infection, disease or other disorder of the body, typically of the upper and/or lower gastrointestinal tract, caused or mediated by H. pylori.
  • An individual having such a gastrointestinal disorder may be symptomatic or asymptomatic.
  • Such disorders include, for example, H.
  • pylori disorders not manifested by the presence of ulcerations in the gastric mucosa, including chronic active or atrophic gastritis, non-ulcer dyspepsia, esophageal reflux disease and gastric motility disorders; and peptic ulcer disease, i.e., H. /?y/ ⁇ rz ' -mediated pre-pyloric, marginal, gastric, duodenal and/or jejunal ulcers.
  • the presence of a gastrointestinal disorder caused or mediated by H. pylori is preferably determined by any of the diagnostic methods recognized and utilized by the medical community. Details concerning such methods are described more fully in the following publications, all of which are incorporated herein by reference in their entireties: Megraud, F., "Diagnosis of Helicobacter pylori Infection", Scandinavian Journal of Gastroenterologv. Supplement, 214: 44-46, 57-60 (1996); Cutler, A. F., "Testing for Helicobacter pylori In Clinical Practice", American Journal of Medicine.
  • the present invention involves administration of bismuth.
  • the quantity of bismuth is by weight of elemental bismuth.
  • bismuth may be in the form of a pharmaceutically- acceptable salt, or may be in the form of an organic complex which contains bismuth as an active ingredient.
  • organic complexes include 2,2'-spirobi [ 1,3,2- benzodoxabismole]. Salts formed between an ⁇ 2 receptor antagonist and a complex of bismuth with a carboxylic acid are not included for use in the present inventions.
  • bismuth is administered in the present methods as a pharmaceutically- acceptable salt.
  • Such bismuth salts include bismuth aluminate, bismuth subcarbonate, bismuth subcitrate, bismuth citrate, tripotassium dicitrato bismuthate, bismuth subgallate, bismuth subnitrate, bismuth tartrate, bismuth subsalicylate, and mixtures thereof.
  • Bismuth citrate, bismuth subcitrate, tripotassium dicitrato bismuthate, bismuth tartrate, bismuth subsalicylate, and mixtures thereof are preferred bismuth salts for use in this invention.
  • the bismuth useful herein may be administered alone, or in combination with other pharmaceutically-acceptable components in a bismuth-containing composition.
  • compositions containing bismuth salts are commercially available.
  • Such compositions include DeNol, containing tripotassium dicitrato bismuthate (by Brocades); Bislumina, containing bismuth aluminate (by Mazuelos); Roter, containing bismuth subnitrate (by Roterpharma); Devrom®, containing bismuth subgallate (by The Parthenon Co., Inc.); and Pepto-Bismol®, containing bismuth subsalicylate (by The Procter & Gamble Company).
  • bismuth may be administered in an amount of from about 50 milligrams to about 5000 milligrams per day, and preferably from about 50 milligrams to about 2500 milligrams, per day, for from about 1 to about 42 days, preferably for up to about 28 days, and most preferably for up to about 14 days.
  • the present invention comprises the administration of bismuth with a non- steroidal anti-inflammatory drug ("NSAID").
  • NSAID non- steroidal anti-inflammatory drug
  • the term "NSAID”, as used herein, refers to any agent which has anti-inflammatory, antipyretic and analgesic properties. Examples of NSAIDs are described in U.S. Patent 4,985,459 to Sunshine et al., issued January 15, 1991, incorporated by reference herein in its entirety.
  • references may be had to standard texts, including Anti- Inflammatory and Anti-Rheumatic Drugs, K. D. Rainsford, Vol. I-III, CRC Press, Boca Raton (1985), and Anti-Inflammatory Agents. Chemistry and Pharmacology. 1 R. A. Scherrer, et al., Academic Press, New York (1974), both of which are incorporated by reference herein.
  • NSAIDs useful in the present invention include, but are not limited to: the oxicams, such as piroxicam, isoxicam, tenoxicam, sudoxicam, and CP-14,304; the salicylates, such as acetylsalicylic acid, disalcid, benorylate, trilisate, safapryn, solprin, diflunisal, and fendosal; the acetic acid derivatives, such as diclofenac, fenclofenac, indomethacin, sulindac, tolmetin, isoxepac, furofenac, tiopinac, zidometacin, acematacin, fentiazac, zomepiract, clidanac, oxepinac, and felbinac; the fenamates, such as mefenamic, meclofenamic, fiufenamic, niflumic, and tolfen
  • NSAIDs useful in the present invention include, but are not limited to: acetylsalicylic acid, ibuprofen, fenbuprofen, fenoprofen, flurbiprofen, indomethacin, ketoprofen, naproxen, their pharmaceutically-acceptable salts, enantiomers thereof, and mixtures thereof.
  • Ibuprofen, indomethacin, acetylsalicylic acid, and naproxen are especially preferred for use in the present invention.
  • NSAIDs are administered in a gastropathic amount.
  • the gastropathic amounts for specific NSAIDs are known in the art. For example, acetylsalicylic acid administered at a levels of about 2.4 to 3.9 grams per day for one week will consistently produce mucosal injury without causing complications.
  • Gastropathic amounts for other NSAIDs are levels which produce comparable gastropathy to the gastropathy produced by the acetylsalicylic acid levels disclosed herein.
  • the duration of NSAID administration is for up to about 14 days, and preferably for from 1 about to about 10 days.
  • the duration of administration should be less than that associated with the development of complications. Therefore, the most preferred duration of administration of the NSAID is from about 1 to about 7 days.
  • the present invention can optionally include one or more antisecretory agents.
  • antisecretory agent refers to agents selected from the group consisting of H2 receptor antagonists, proton pump inhibitors, and mixtures thereof. These agents are administered in a therapeutically effective amount.
  • therapeutically effective amount refers to a level which is commonly known in the art and recognized and utilized by the medical community. Such an amount will vary depending on the particular agent(s) administered, the size and/or condition of the individual receiving treatment or other medical factors determined by the administering physician.
  • H2 receptor antagonists are disclosed fully in U.S. Patent No. 5,294,433 to Singer et al., issued March 15, 1994, incorporated herein by reference in its entirety.
  • Preferred H2 receptor antagonists include cimetidine, etintidine, ranitidine, ICIA-5165, tiotidine, ORF-17578, luptidine, donetidine, famotidine, rozatidine, pifatidine, lamtidine, BL-6548, BMY-25271, zaltidine, nizatidine, mifentidine, BMY-52368,SKF- 94482, BL-6341A, ICI-162846, ramixotidine, Wy-45727, SR-58042, BMY-25405, loxidine, DA-4634, bisfentidine, sufotidine, ebrotidine, HE-30-256,D-16637, FRG- 8813, FRG-8701, impromidine, L
  • Preferred for use in the present invention are cimetidine, ranitidine, famotidine, roxatidine, nizatidine, mifentidine, and mixtures thereof. Most preferred are cimetidine and ranitidine.
  • Proton pump inhibitors are described in greater detail in the following publications, which are incorporated by reference herein in their entireties: U.S. Patent No. 4,786,505 to Lovgren, issued November 22, 1988; U. S. Patent No. 4,255,431 to Junggren, issued March 10, 1981 ; and U.S. Patent No. 4,853,230 to Lovgren, issued August 1, 1989.
  • Preferred for use in the present invention are omeprazole, lansoprazole, pantoprazole, and mixtures thereof. Most preferred is omeprazole.
  • Antisecretory agents may be administered for from about 1 to about 42 days, preferably for up to about 28 days, and most preferably for up to about 14 days.
  • Pharmaceutically Acceptable Carriers may be administered for from about 1 to about 42 days, preferably for up to about 28 days, and most preferably for up to about 14 days.
  • compositions of the present invention may contain optional components which affect the physical and therapeutic characteristics of the present compositions.
  • a variety of pharmaceutically-acceptable carriers and excipients may be included, depending upon the particular dosage form to be used.
  • Various oral dosage forms can be used, including such solid forms as tablets, capsules, granules and bulk powders. Tablets can be compressed, tablet triturates, enteric-coated, sugar coated, film-coated or multiple compressed, containing suitable binders, lubricants, diluents, disintegrating agents, coloring agents, flavoring agents, flow-inducing agents and melting agents.
  • Liquid oral dosage forms include aqueous solutions, emulsions, suspensions, solutions, and/or suspensions reconstituted from non-effervescent granules and effervescent preparations reconstituted from effervescent granules, containing suitable solvents, preservatives, emulsifying agents, suspending agents, diluents, sweeteners, melting agents, coloring, and flavoring agents.
  • compositions of this invention may be used according to the methods of this invention by administering the composition from 1 to 4 times per day, and preferably from 1 to 2 times per day; for from 1 to 28 days, preferably for from about 1 to about 21 days, and most preferably for from about 1 to about 14 days.
  • the specific frequency of administration will depend upon such factors as the specific NSAID, bismuth compound or composition and antimicrobial(s) used, the levels at which the components are incorporated in the composition, the nature and severity of the condition to be treated, and the nature of any concurrent therapy, if any.
  • the methods of the present invention comprise the treatment of a human or lower animal subject having a gastrointestinal disorder caused or mediated by Helicobacter pylori comprising administering to the subject bismuth and a non-steroidal anti-inflammatory drug (hereinafter referred to as "NSAID").
  • NSAID non-steroidal anti-inflammatory drug
  • the present method may further comprise the administration of one or more antisecretory agents.
  • administering refers to any method which, in sound medical practice delivers the compounds or compositions used in this invention to the subject to be treated in such a manner so as to be effective in the treatment of the gastrointestinal disorder.
  • the bismuth, NSAID, and antisecretory agent(s), if present, are administered orally.
  • the present invention encompasses methods wherein the administering of bismuth, the NSAID, and optionally the antisecretory agent(s) are performed simultaneously (beginning and ending on the same day), concurrently (overlapping but not of the same duration of administration), or consecutively (sequential, but where the course of treatment is substantially continuous).
  • the bismuth and NSAID are administered concurrently and administration for both bismuth and the NSAID is commenced on the same day.
  • one or more antisecretory agents are also present, it is preferred that the bismuth and the antisecretory agent(s) are administered simultaneously.
  • An asymptomatic young volunteer identified as having H pylori infection through the results of a mass screening is treated by a method of the present invention.
  • the subject is orally administered approximately 2500 milligrams of bismuth in the form of bismuth subsalicylate daily, (sold by The Procter & Gamble Company under the name "Pepto-Bismol®"), in four equal doses, for 28 days; and approximately 100- 200 milligrams of indomethacin daily, in four equal doses, for about 14 days.
  • a diagnostic test performed on the volunteer shows no evidence of H. pylori.
  • a human subject is suffering from chronic active gastritis.
  • a diagnostic test reveals the presence of H. pylori.
  • the individual is treated by orally administering approximately 500 milligrams of bismuth daily in the form of bismuth subcitrate ("DeNol", sold by Brocades), in two equal doses, for about 28 days; approximately 3.9 grams of acetylsalicylic acid daily, in three equal doses, for about 14 days; and approximately 20 milligrams of omeprazole daily, for 28 days.
  • Administration of all three agents is commenced on the same day. One to two months later, the diagnostic test is repeated. The results show no evidence of H. pylori.
  • EXAMPLE III EXAMPLE III
  • a human subject is suffering from non-ulcer dyspepsia.
  • a biopsy of the gastric mucosa is taken from the stomach of the subject. Analysis of the biopsy sample indicates the presence of urease in the sample and the presence of H pylori in the stomach of the subject.
  • the subject is given approximately 1200 milligrams of bismuth daily, (administered as bismuth subsalicylate in the composition Pepto-Bismol®, sold by The Procter & Gamble Company), in four equal doses, for about 21 days; 1200-3200 milligrams of ibuprofen daily, in three to four equal doses, for about 7 days; and 150 milligrams of ranitidine daily, in two equal doses, for about 21 days. Administration of all three agents is commenced on the same day. A biopsy sample taken and analyzed one to two months later shows no evidence of H. pylori.

Landscapes

  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne des méthodes et des compositions pour traiter les troubles gastro-intestinaux provoqués par Helicobacter pylori, contenant du bismuth et une quantité gastropathique d'un médicament anti-inflammatoire non stéroïdien. La composition peut également contenir une quantité suffisante pour avoir un effet thérapeutique, d'un ou de plusieurs médicaments anti-sécrétoires.
PCT/US1997/021462 1996-11-22 1997-11-21 Compositions et methodes pour traiter des troubles gastro-intestinaux WO1998022118A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
HU9904073A HUP9904073A3 (en) 1996-11-22 1997-11-21 Compositions for the treatment of gastrointestinal disorders containing bismuth and nsaid
EP97949569A EP0941102A1 (fr) 1996-11-22 1997-11-21 Compositions et methodes pour traiter des troubles gastro-intestinaux
CA002271381A CA2271381A1 (fr) 1996-11-22 1997-11-21 Compositions et methodes pour traiter des troubles gastro-intestinaux
NO992468A NO992468L (no) 1996-11-22 1999-05-21 Sammensetning for behandling av gastrointestinale forstyrrelser inneholdende vismut og NSAID

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US75551796A 1996-11-22 1996-11-22
US08/755,517 1996-11-22

Publications (1)

Publication Number Publication Date
WO1998022118A1 true WO1998022118A1 (fr) 1998-05-28

Family

ID=25039481

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/021462 WO1998022118A1 (fr) 1996-11-22 1997-11-21 Compositions et methodes pour traiter des troubles gastro-intestinaux

Country Status (7)

Country Link
EP (1) EP0941102A1 (fr)
CN (1) CN1238694A (fr)
CA (1) CA2271381A1 (fr)
HU (1) HUP9904073A3 (fr)
NO (1) NO992468L (fr)
TR (1) TR199901101T2 (fr)
WO (1) WO1998022118A1 (fr)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1154771A1 (fr) * 1999-02-26 2001-11-21 Nitromed, Inc. Inhibiteurs de la pompe a proton nitroses et nitrosyles, compositions et procedes d'utilisation
US6365184B1 (en) 1996-01-08 2002-04-02 Astrazeneca Ab Oral pharmaceutical dosage forms comprising a proton pump inhibitor and a NSAID
EP1300148A2 (fr) * 2001-08-27 2003-04-09 Hedonist Biochemical Technologies Inc. Utilisation du gallate de bismuth pour l'inhibition de la production de l'oxyde nitrique synthase
US7211590B2 (en) 2002-08-01 2007-05-01 Nitromed, Inc. Nitrosated proton pump inhibitors, compositions and methods of use
US7332505B2 (en) 1999-02-26 2008-02-19 Nitromed, Inc. Nitrosated and nitrosylated proton pump inhibitors, compositions and methods of use
EP1977751A1 (fr) * 1999-06-17 2008-10-08 Takeda Pharmaceutical Company Limited Utilisation de (r)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-piridinyl]methyl]sulfinyl]-1h-benzimidazole cristallin pour la preparation de compositions pharmaceutiques
EP2345650A1 (fr) * 2000-12-01 2011-07-20 Takeda Pharmaceutical Company Limited (R)-2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole amorphe comme agent anti-ulcère
US8222422B2 (en) 2008-03-10 2012-07-17 Takeda Pharmaceutical Company Limited Crystal of benzimidazole compound
US8697097B2 (en) 2002-10-16 2014-04-15 Takeda Pharmaceutical Company Limited Stable solid preparations
US8852636B2 (en) 2001-06-01 2014-10-07 Pozen Inc. Pharmaceutical compositions for the coordinated delivery of NSAIDs
US8945621B2 (en) 2009-06-25 2015-02-03 Pozen Inc. Method for treating a patient at risk for developing an NSAID-associated ulcer
US9220698B2 (en) 2008-09-09 2015-12-29 Pozen Inc. Method for delivering a pharmaceutical composition to patient in need thereof
US9238029B2 (en) 2004-06-16 2016-01-19 Takeda Pharmaceuticals U.S.A., Inc. Multiple PPI dosage form
US9539214B2 (en) 2011-12-28 2017-01-10 Pozen Inc. Compositions and methods for delivery of omeprazole plus acetylsalicylic acid

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101148399B1 (ko) * 2005-06-22 2012-05-23 일양약품주식회사 항궤양제 및 점막보호제를 함유하는 경구용 위장질환치료용 약제 조성물
WO2023143573A1 (fr) * 2022-01-30 2023-08-03 上海石趣医药科技有限公司 Utilisation d'un composé contenant du bismuth dans un traitement de maladies

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0437294A1 (fr) * 1990-01-09 1991-07-17 Yamanouchi Europe B.V. Compositions pharmaceutiques orales sous forme de doses unitaires
WO1992011849A1 (fr) * 1991-01-14 1992-07-23 The Procter & Gamble Company Compositions pharmaceutiques absorbables
WO1993009784A1 (fr) * 1991-11-22 1993-05-27 The Procter & Gamble Company Preparation pharmaceutique de doses unitaires de subsalicylate de bismuth
GB2262036A (en) * 1991-12-06 1993-06-09 Glaxo Group Ltd Anti inflammatories or analgesics

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0437294A1 (fr) * 1990-01-09 1991-07-17 Yamanouchi Europe B.V. Compositions pharmaceutiques orales sous forme de doses unitaires
WO1992011849A1 (fr) * 1991-01-14 1992-07-23 The Procter & Gamble Company Compositions pharmaceutiques absorbables
WO1993009784A1 (fr) * 1991-11-22 1993-05-27 The Procter & Gamble Company Preparation pharmaceutique de doses unitaires de subsalicylate de bismuth
GB2262036A (en) * 1991-12-06 1993-06-09 Glaxo Group Ltd Anti inflammatories or analgesics

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
TANAKA S ET AL: "Indomethacin increases mucus bismuth concentration in ranitidine bismuth citrate treated rats", GASTROENTEROLOGY, 108 (4 SUPPL.). 1995. A234., XP002059838 *

Cited By (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6613354B2 (en) 1996-01-08 2003-09-02 Astrazeneca Ab Oral pharmaceutical dosage forms comprising a proton pump inhibitor and a NSAID
US6365184B1 (en) 1996-01-08 2002-04-02 Astrazeneca Ab Oral pharmaceutical dosage forms comprising a proton pump inhibitor and a NSAID
US7488497B2 (en) 1996-01-08 2009-02-10 Astrazeneca Ab Oral pharmaceutical dosage forms comprising a proton pump inhibitor and a NSAID
US8114435B2 (en) 1996-01-08 2012-02-14 Astrazeneca Ab Oral pharmaceutical dosage forms comprising a proton pump inhibitor and a NSAID
EP1154771A1 (fr) * 1999-02-26 2001-11-21 Nitromed, Inc. Inhibiteurs de la pompe a proton nitroses et nitrosyles, compositions et procedes d'utilisation
EP1154771A4 (fr) * 1999-02-26 2005-04-20 Nitromed Inc Inhibiteurs de la pompe a proton nitroses et nitrosyles, compositions et procedes d'utilisation
US7332505B2 (en) 1999-02-26 2008-02-19 Nitromed, Inc. Nitrosated and nitrosylated proton pump inhibitors, compositions and methods of use
US8884019B2 (en) 1999-06-17 2014-11-11 Takeda Pharmaceutical Company Limited Benzimidazole compound crystal
EP1977751A1 (fr) * 1999-06-17 2008-10-08 Takeda Pharmaceutical Company Limited Utilisation de (r)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-piridinyl]methyl]sulfinyl]-1h-benzimidazole cristallin pour la preparation de compositions pharmaceutiques
US9145389B2 (en) 1999-06-17 2015-09-29 Takeda Pharmaceutical Company Limited Benzimidazole compound crystal
US7569697B2 (en) 1999-06-17 2009-08-04 Takeda Pharmaceutical Company Limited Benzimidazole compound crystal
US7737282B2 (en) 1999-06-17 2010-06-15 Takeda Pharmaceutical Company Limited Benzimidazole compound crystal
US8552198B2 (en) 1999-06-17 2013-10-08 Takeda Pharmaceutical Company Limited Benzimidazole compound crystal
US8030333B2 (en) 1999-06-17 2011-10-04 Takeda Pharmaceutical Company Limited Benzimidazole compound crystal
EP2345650A1 (fr) * 2000-12-01 2011-07-20 Takeda Pharmaceutical Company Limited (R)-2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole amorphe comme agent anti-ulcère
US9707181B2 (en) 2001-06-01 2017-07-18 Pozen Inc. Pharmaceutical compositions for the coordinated delivery of NSAIDs
US9198888B2 (en) 2001-06-01 2015-12-01 Pozen Inc. Pharmaceutical compositions for the coordinated delivery of NSAIDs
US9364439B2 (en) 2001-06-01 2016-06-14 Pozen Inc. Pharmaceutical compositions for the coordinated delivery of NSAIDs
US8852636B2 (en) 2001-06-01 2014-10-07 Pozen Inc. Pharmaceutical compositions for the coordinated delivery of NSAIDs
US8858996B2 (en) 2001-06-01 2014-10-14 Pozen Inc. Pharmaceutical compositions for the coordinated delivery of NSAIDS
US8865190B2 (en) 2001-06-01 2014-10-21 Pozen Inc. Pharmaceutical compositions for the coordinated delivery of NSAIDs
US9345695B2 (en) 2001-06-01 2016-05-24 Pozen Inc. Pharmaceutical compositions for the coordinated delivery of NSAIDs
US9161920B2 (en) 2001-06-01 2015-10-20 Pozen Inc. Pharmaceutical compositions for the coordinated delivery of NSAIDs
EP1300148A3 (fr) * 2001-08-27 2003-05-21 Hedonist Biochemical Technologies Inc. Utilisation du gallate de bismuth pour l'inhibition de la production de l'oxyde nitrique synthase
EP1300148A2 (fr) * 2001-08-27 2003-04-09 Hedonist Biochemical Technologies Inc. Utilisation du gallate de bismuth pour l'inhibition de la production de l'oxyde nitrique synthase
US7211590B2 (en) 2002-08-01 2007-05-01 Nitromed, Inc. Nitrosated proton pump inhibitors, compositions and methods of use
US8697094B2 (en) 2002-10-16 2014-04-15 Takeda Pharmaceutical Company Limited Stable solid preparations
US9265730B2 (en) 2002-10-16 2016-02-23 Takeda Pharmaceutical Company Limited Stable solid preparations
US8697097B2 (en) 2002-10-16 2014-04-15 Takeda Pharmaceutical Company Limited Stable solid preparations
US9238029B2 (en) 2004-06-16 2016-01-19 Takeda Pharmaceuticals U.S.A., Inc. Multiple PPI dosage form
US9889152B2 (en) 2004-06-16 2018-02-13 Takeda Pharmaceuticals U.S.A., Inc. Multiple PPI dosage form
US8222422B2 (en) 2008-03-10 2012-07-17 Takeda Pharmaceutical Company Limited Crystal of benzimidazole compound
US9220698B2 (en) 2008-09-09 2015-12-29 Pozen Inc. Method for delivering a pharmaceutical composition to patient in need thereof
US9393208B2 (en) 2008-09-09 2016-07-19 Pozen Inc. Method for delivering a pharmaceutical composition to patient in need thereof
US9801824B2 (en) 2008-09-09 2017-10-31 Pozen Inc. Method for delivering a pharmaceutical composition to patient in need thereof
US8945621B2 (en) 2009-06-25 2015-02-03 Pozen Inc. Method for treating a patient at risk for developing an NSAID-associated ulcer
US9539214B2 (en) 2011-12-28 2017-01-10 Pozen Inc. Compositions and methods for delivery of omeprazole plus acetylsalicylic acid
US9987231B2 (en) 2011-12-28 2018-06-05 Pozen Inc. Compositions and methods for delivery of omeprazole plus acetylsalicylic acid
US10603283B2 (en) 2011-12-28 2020-03-31 Genus Lifesciences, Inc. Compositions and methods for delivery of omeprazole plus acetylsalicylic acid

Also Published As

Publication number Publication date
CA2271381A1 (fr) 1998-05-28
CN1238694A (zh) 1999-12-15
NO992468L (no) 1999-07-01
EP0941102A1 (fr) 1999-09-15
HUP9904073A2 (hu) 2000-03-28
NO992468D0 (no) 1999-05-21
TR199901101T2 (xx) 1999-07-21
HUP9904073A3 (en) 2000-04-28

Similar Documents

Publication Publication Date Title
WO1998022118A1 (fr) Compositions et methodes pour traiter des troubles gastro-intestinaux
WO1998022117A1 (fr) Compositions de traitement de troubles gastro-intestinaux contenant du bismuth, des anti-inflammatoires non steroidiens ainsi qu'un ou plusieurs agents anti-microbiens et methodes correspondantes
JP2648327B2 (ja) 胃腸疾患を治療するための組成物及び方法
Reimer Safety of long-term PPI therapy
Quan et al. Sestrin2 prevents age-related intolerance to post myocardial infarction via AMPK/PGC-1α pathway
Chey et al. Lansoprazole and Ranitidine Affect the Accuracy of the 14 C-Urea Breath Test by a pH-Dependent Mechanism.
EP0206626B1 (fr) Utilisation de bismuth pour la fabrication d'un médicament destiné au traitement des désordres gastrointestinaux dûs à Campylobacter polyridis
CA2635272C (fr) Inhibiteur agissant rapidement de la secretion acide gastrique
Laursen et al. Omeprazole in the long-term treatment of gastro-oesophageal reflux disease: a double-blind randomized dose-finding study
Roesler et al. Eradication treatment of Helicobacter pylori infection: its importance and possible relationship in preventing the development of gastric cancer
Salmon et al. Evaluation of colloidal bismuth (De-Nol) in the treatment of duodenal ulcer employing endoscopic selection and follow up
Bough Jr et al. Gastroesophageal reflux laryngitis resistant to omeprazole therapy
Cohen et al. Mechanism of aspirin injury to human gastroduodenal mucosa
Sarosiek et al. Significant increase of esophageal mucin secretion in patients with reflux esophagitis after healing with rabeprazole: its esophagoprotective potential
Barragry et al. Giant gastric ulcers. A review of 49 cases.
WO1982000762A1 (fr) Agent pour canal d'alimentation
Marks, IN & Girdwood Recurrence of duodenal ulceration in patients on maintenance sucralfate-a 12-month follow-up study
RU2646450C1 (ru) Способ лечения предраковых и ранних стадий раковых заболеваний желудка
Scarpignato et al. Inhibition of gastric emptying and secretion by pirenzepine and atropine in rats
Ozalp et al. Evaluation of risk factors for mortality in perforated peptic ulcer in Ankara Numune Teaching Hospital, Ankara, Turkey
Yamamoto et al. Cyclooxygenase-2: from arthritis treatment to new indications for the prevention and treatment of cancer.
Parente et al. Colloidal Bismuth Subcitrate and Ranitidne in the Short-Term Treatment of Benign Gastric Ulcer an Endoscopically Controlled Trial
Dalzell et al. Treatment of refractory ulcerative oesophagitis with omeprazole.
CASTLES et al. Peptic ulcer and gastrin in pigs
Borrie Unsuspected Oesophageal Leiomyoma Found at Hiatal Herniorrhaphy

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 97199982.1

Country of ref document: CN

AK Designated states

Kind code of ref document: A1

Designated state(s): CA CN CZ HU NO TR

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
ENP Entry into the national phase

Ref document number: 2271381

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 1999/01101

Country of ref document: TR

WWE Wipo information: entry into national phase

Ref document number: PV1999-1808

Country of ref document: CZ

WWE Wipo information: entry into national phase

Ref document number: 1997949569

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1997949569

Country of ref document: EP

WWR Wipo information: refused in national office

Ref document number: PV1999-1808

Country of ref document: CZ

WWW Wipo information: withdrawn in national office

Ref document number: 1997949569

Country of ref document: EP